What is Thrombotic Thrombocytopenic Purpura?

At the outset, it is important to note there are two basic types of TTP, having nothing to do with each other. Thrombotic thrombocytopenic purpura (TTP) is a rare blood condition characterized by the formation of small clots (thrombi) within the circulation, which results in the consumption of platelets and thus a low platelet count (thrombocytopenia). A different TTP-like syndrome, more properly called hemolytic uremic syndrome (HUS) or “adult-HUS,” is caused by the specific bacterium E. coli O157:H7. HUS is a rare complication of E. coli O157:H7 infections and usually occurs in young children. But when it occurs in adults, doctors often refer to it as TTP or TTP/HUS because of its resemblance to TTP.

True TTP has nothing to do with the E. coli O157:H7 bacterium. It instead occurs as the result of the lack of an enzyme in the plasma portion of the blood that is responsible for cleaving, or cutting up, a large molecule called Von Willebrand factor (vWF) that is involved in blood clot formation. In true TTP, a lack of this enzyme allows ultra large vWF molecules to circulate in the blood and leads to the inappropriate formation of platelet clumps (thrombi) particularly within blood vessels supplying the brain and kidneys. These give rise to the typical symptoms of TTP. HUS, on the other hand, also involves the formation of micro-thrombi, but through a process that does not involve abnormal vWF activity. The treatment for true TTP involves plasma exchange, which is done in an effort to replace the enzyme that cleaves vWF. In HUS, plasma exchange is unnecessary, but dialysis is often done when the kidneys fail to filter normally due to the presence of micro-thrombi within the tiny blood vessels at the heart of the kidneys filtering units.

A History of the Clinical Recognition of Thrombotic Thrombocytopenic Purpura:

The first case of TTP was described by Moschcowitz, in 1925, in which a 16 year old female was admitted to the hospital with an acute and fatal illness that included stroke and heart failure. At autopsy, small arterioles in many organs were occluded by hyaline thrombi. In 1936, the subsequent report of 4 cases of disseminated arteriolar and capillary platelet thrombosis, by Baehr et al. established Thrombotic Thrombocytopenic Purpura as a clinical entity and identified thrombocytopenia as a central feature of the disease process. There was some mention of renal abnormalities in both of these studies. However, in 1961 the renal abnormalities of TTP were more clearly described as an important feature, and were subsequently confirmed by Bukowski and Koblenzer in 1962. Thereafter, the emphasis of reports on Thrombotic Thrombocytopenic Purpura was almost uniformly on the triad, consisting of thrombocytopenia purpura, hemolytic anemia, and varying neurologic manifestations. Then, in 1966, Amorosi and Ultmann described the diagnostic pentad of thrombocytopenia, microangiopathic hemolytic anemia, neurologic signs and symptoms, renal dysfunction, and fever.

Hemolytic Uremic Syndrome (HUS) was first described by Gasser et al. in 1955. The characteristic features of this syndrome include thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure, resulting in renal necrosis in children. Thrombotic Thrombocytopenic Purpura involves the characteristic lesion of renal thrombotic microangiopathy seen in HUS and has even been called the “adult” HUS.

Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome were once thought to represent opposite ends of the spectrum of the same disease process and are classified by some as thrombotic microangiopathy (TMA). There is considerable overlap of the clinical and laboratory findings between these two syndromes, the difference mainly in the age of the patients, predominance of neurologic findings, and the severity of renal involvement. These clinical syndromes have substantially changed since their initial recognition and description and are now described by most as a single syndrome - the same disease with different clinical expressions, characterized by microangiopathy, hemolytic anemia, renal failure, and sometimes, neurologic involvement. It has been determined that few patients have the full pentad of thrombocytopenia, hemolysis, neurologic signs, renal failure, and fever.

The syndrome of Thrombotic Thrombocytopenic Purpura has been described as “rare,” “unusual,” and “infrequent.” But as early as 1968 (after publishing a study involving over 300 patients with TTP), Silverstein concluded that “the condition can no longer be considered rare.” Prior to his investigation, 11 individual studies had been done by others, involving a total of 795 patients.

Classification of Thrombotic Thrombocytopenic Purpura:

The causes of true TTP are not fully understood, but risk factors include certain drugs, pregnancy, certain viral infections, and malignancies. There is also a childhood form that is genetic. Patients are considered to have “primary” Thrombotic Thrombocytopenic Purpura if they have no clinically apparent illness that is recognized to be associated with this syndrome. 

In an attempt to identify the other subsets of patients with TTP with similar characteristics, several classifications have been proposed:

• infantile and childhood Thrombotic Thrombocytopenic Purpura not associated with an infectious episode, but presenting with a diarrheal Prodrome with glomerular thrombotic microangiopathy as the primary pathologic feature, but with a good prognosis;
  
  
• hereditary and recurrent TTP in children and adults, in which microangiopathy in the kidney is predominantly arterial, and hypertension is often severe;
  
  
• post infectious Thrombotic Thrombocytopenic Purpura, which follows a clinically obvious infection, occurs at any age, and is usually due to Shigella, Salmonella, E. coli O157:H7, or streptococcus;
  
  
• TTP accompanying vascular collagen diseases, such as systemic lupus erythematous or scleroderma;
  
  
• TTP associated with pregnancy or drugs.

>>Symptoms of TTP>>